3,5-Dimethylpyridine → rac-(3R,5S)-3,5-dimethylpiperidine hydrochloride

Temperature

5 °C

3,5-Lutidine (6475.0 g.) is hydrogenated under 1000 psi hydrogen pressure in ethanol using 1665 g. of 5% rhodium on carbon catalyst (50% H2O) at room temperature. The catalyst is filtered off and anhydrous hydrogen chloride bubbled into the filtrate at a temperature below 40° C. until the solution is strongly acidic. The solution is then concentrated in vacuo to a thick slurry which is diluted with 40 liters of hexane. The crystalline material is filtered off and dried in the atmosphere to give 8.9 kg. of crude product. The crude 3,5-dimethylpiperidine hydrochloride is dissolved in 14 liters of water and the pH of this solution adjusted to 7.0 with dilute sodium hydroxide solution. The mixture is washed with 7 l. and then with 3 l. of chloroform to remove unreduced 3,5-lutidine. The aqueous solution is then adjusted to pH 12-13 by the addition of 40% sodium hydroxide solution and extracted with 6 l. and then with 3 l. of chloroform. The combined chloroform extract is dried over anhydrous magnesium sulfate and chilled to 5° C. in an ice bath. Anhydrous hydrogen chloride is then injected until the solution is strongly acidic. The chloroform solution is concentrated in vacuo as benzene is continuously added. When most of the chloroform has been replaced, the product is filtered from about 36 l. of benzene. The filter cake is washed with cold benzene and hexane, and air dried, to obtain 4.8 kg. of product, m.p. 222°-224° C.

1. customat room temperature
2. filtrationThe catalyst is filtered off
3. customanhydrous hydrogen chloride bubbled into the filtrate at a temperature below 40° C. until the solution
4. concentrationThe solution is then concentrated in vacuo to a thick slurry which
5. additionis diluted with 40 liters of hexane
6. filtrationThe crystalline material is filtered off
7. customdried in the atmosphere
8. customto give 8.9 kg
9. washThe mixture is washed with 7 l
10. customof chloroform to remove unreduced 3,5-lutidine
11. additionThe aqueous solution is then adjusted to pH 12-13 by the addition of 40% sodium hydroxide solution
12. extractionextracted with 6 l
13. extractionThe combined chloroform extract
14. dry with materialis dried over anhydrous magnesium sulfate
15. concentrationThe chloroform solution is concentrated in vacuo as benzene
16. additionis continuously added
17. filtrationthe product is filtered from about 36 l
18. washThe filter cake is washed with cold benzene and hexane, and air
19. customdried
20. customto obtain 4.8 kg

ORD record

ord-89156f3ad6ad4574958ba276c74e12dc

Source dataset

uspto-grants-1978_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04124590